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WEDNESDAY,
Dec. 7, 2011 (HealthDay News) — Multiple sclerosis may
begin in the outer layer of the brain and work its way into the deep interior,
according to a new study that upends long-held beliefs about the nervous
system disease.

The new findings, which
could spur changes in the way MS is diagnosed and treated, appear to solidify a
theory that's emerged in recent years. This new premise suggests that gray
matter, the outer covering of the brain called the cortex, and the fluid that
surrounds and cushions it, is where MS originates, not in the bulky white
matter that composes most of the brain's core.

It's an
"outside-in" process in other words, said study co-author Dr. Claudia
Lucchinetti, a professor of neurology at the Mayo Clinic in Rochester, Minn.

"We already recognized
before this study that the cortex — the superficial layer where cells
control memory, attention, and other key pathways in the nervous system
— was involved in MS. But most of what we knew came from autopsy
studies, from patients who had longstanding disease, 30 to 50 years," said
Lucchinetti. The new findings show the cortex is involved early on and may even
be the initial target of the disease, she added.

Lucchinetti and her colleagues
analyzed brain tissue of early MS patients obtained through biopsies. The
tissue was primarily white matter, but about one-fourth of the biopsies (138 of
563 patient screenings) also included tiny fragments of cortex. The scientists
used that tissue as the focus of their study.

The cortical tissues were
viewed on a microscopic level. "The early lesions were highly
inflammatory," said Lucchinetti, whose research is published in the Dec. 8
issue of the New England Journal of Medicine.

The authors also noted that
inflammation was also present in the meninges, the protective membranes that
cover the surface of the brain and spinal cord, and was strongly associated
with inflammation in the cortex tissue.

About 400,000 Americans
have MS, according to the National Multiple Sclerosis Society. Its cause is
unknown, but it is believed to occur when the body's immune system chips away
at the protective myelin sheath, a fatty insulator that covers nerves, and it can be debilitating. Symptoms can include weakness and numbness,
paralysis, poor vision, fatigue, dizziness, and tremor. Its severity varies
widely in patients, said Lucchinetti.

Lucchinetti said if
scientists can understand the genesis of the disease, better diagnostic
procedures and treatments could be developed.

"The findings are
provocative," said Dr. Peter Calabresi, professor of neurology and
director of the MS Center at Johns Hopkins Hospital, who wrote an accompanying
editorial.

"It's an exciting
study. For many years we thought MS was predominantly a disease of the white
matter. More recently people have found there are some changes in the gray
matter. This is the first time that anyone has definitively shown
there's extensive inflammation in the gray matter early on in the
disease," said Calabresi.

Calabresi likens the
findings to leaves on a tree. "Everyone thought the attack was on the
leaves, the white matter, but now people think it's more likely the
trunk," he said.

Should patients get
excited?

Dr. Jerome Graber, an
assistant professor of neurology at Albert Einstein College of Medicine in the
Bronx, N.Y., said it's a good study, but suggests no immediate clinical
benefits. "My answer to my patients is that it doesn't have an immediate
implication for them yet. I have no new treatment
for you because of this study. But I think it opens a lot of doors for
researchers to ask a whole new set of questions," he said. And the link
with the meninges is also intriguing, he said.

Calabresi agreed it offers
hope. "I think it gives us a lot of hope," he said. "It gives us
yet one more tool to follow the disease. There's a mysterious aspect to MS.
It's hard to quantify. But now we know gray matter is definitely involved, and
we can track it and see if a therapy is working or not, and if not, move on to
the next therapy."

Ultimately, this research
"will allow us to understand [MS] better and track and treat it
better," he said.

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